ArticleClinical pharmacokinetics2020
A Physiologically Based Pharmacokinetic Model of Voriconazole Integrating Time-Dependent Inhibition of CYP3A4, Genetic Polymorphisms of CYP2C19 and Predictions of Drug-Drug Interactions.
Article in Clinical pharmacokinetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- Co-Administration with Voriconazole Doubles the Exposure of Ruxolitinib in Patients with Hematological Malignancies.Drug design, development and therapy · 2022Trial
- Physiologically based pharmacokinetic (PBPK) modelling of tamsulosin related to CYP2D6*10 allele.Archives of pharmacal research · 2021Trial
- Assessing the Influence of CYP3A4 Inhibitors on Voriconazole Exposure across CYP2C19 Genotypes: A Physiologically Based Pharmacokinetic Model Analysis.Clinical pharmacokinetics · 2026Article
- Development of an isavuconazole physiologically-based pharmacokinetic model for adult and pediatric populations.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Optimizing ribociclib dosing in breast cancer with brain metastasis patients using a physiologically based pharmacokinetic model.BMC cancer · 2026Article
- Comparative pharmacokinetics of voriconazole between elderly and young adult patients: a population pharmacokinetic study.Journal of pharmaceutical policy and practice · 2026Article
- An Interpretable PK-Informed Hybrid Model for Voriconazole Exposure Prediction: Roles of CYP2C19 Genotype and Inflammation.Drug design, development and therapy · 2026Article
- Mechanistic insights into voriconazole-exacerbated selpercatinib-induced thrombocytopenia: a pharmacokinetic interaction case report.Frontiers in oncology · 2026Article
- Repeated voriconazole therapeutic drug monitoring in hospitalised patients: a real-world cohort study of out-of-range exposure and concentration response to dose adjustment.Frontiers in pharmacology · 2026Article
- A Drug-Drug Interaction of Ainuovirine with Fluconazole in Healthy Adults and Dose Optimization Informed by Pharmacokinetics Modelling.Drug design, development and therapy · 2026Article
- Review
- Development of Voriconazole Proliposome Based Dry Powder for Inhalation: A Design of Experiment Approach.Pharmaceutics · 2025Article
- Physiologically based pharmacokinetic modeling supports investigation of potential drug-drug interactions in the pre- and early post-hematopoietic stem cell transplantation stages.Frontiers in pharmacology · 2025Article
- A physiologically-based pharmacokinetic precision dosing approach to manage dasatinib drug-drug interactions.CPT: pharmacometrics & systems pharmacology · 2024Article
- Voriconazole: a review of adjustment programs guided by therapeutic drug monitoring.Frontiers in pharmacology · 2024Review
- Exploring inter-ethnic and inter-patient variability and optimal dosing of osimertinib: a physiologically based pharmacokinetic modeling approach.Frontiers in pharmacology · 2024Article
- Factors affecting voriconazole concentration to dose ratio changes according to route of administration.European journal of hospital pharmacy : science and practice · 2023Article
- Pharmacokinetic and Pharmacodynamic Drug-Drug Interactions: Research Methods and Applications.Metabolites · 2023Review
- Article
- Physiologically based pharmacokinetic modeling of tacrolimus for food-drug and CYP3A drug-drug-gene interaction predictions.CPT: pharmacometrics & systems pharmacology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVoriconazole, a first-line antifungal drug, exhibits nonlinear pharmacokinetics (PK), together with large interindividual variability but a narrow therapeutic range, and markedly inhibits cytochrome P450 (CYP) 3A4 in vivo. This causes difficulties in selecting appropriate dosing regimens of voriconazole and coadministered CYP3A4 substrates.
objectiveThis study aimed to investigate the metabolism of voriconazole in detail to better understand dose- and time-dependent alterations in the PK of the drug, to provide the model basis for safe and effective use according to CYP2C19 genotype, and to assess the potential of voriconazole to cause drug-drug interactions (DDIs) with CYP3A4 substrates in more detail.
methodsIn vitro assays were carried out to explore time-dependent inhibition (TDI) of CYP3A4 by voriconazole. These results were combined with 93 published concentration-time datasets of voriconazole from clinical trials in healthy volunteers to develop a whole-body physiologically based PK (PBPK) model in PK-Sim
resultsThe result of the half maximal inhibitory concentration (IC
conclusionsBoth the in vitro assay and model-based simulations support TDI of CYP3A4 by voriconazole as a pivotal characteristic of this drug's PK. The PBPK model developed here could support individual dose adjustment of voriconazole according to genetic polymorphisms of CYP2C19, and DDI risk management. The applicability of modeling results for patients remains to be confirmed in future studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.